Purpose :
To investigate the genetic mutation characteristics as well as the genotype-phenotype relations in patients with TGFBI gene-associated corneal dystrophy.

Methods :
All patients received detailed clinical examination, including determining the best- corrected visual acuity (BCVA) with the Binocular International Standard Visual Acuity Chart (snellen visual acuity), and examining the anterior segment with the slit-lamp microscope; and some patients received corneal confocal laser scanning microscopy (HRT). TGFBI gene amplification and direct sequencing were conducted on the genome DNA of 73 cases of patients with corneal dystrophy through the polymerase chain reaction (PCR) technique.

Results :
Nine kinds of TGFBI gene heterozygosis missense mutations were detected in 54 patients, including 8 reported pathogenic mutations: c.371G>A(p.R124H), c.370C>T(p.R124C),c.371G>T(p.R124L),c.1663C>T(p.R555W),c.1664G>A(p.R555Q),c.1514T>A(p.V505D),c.1859C>A(p.A620D), c.1877A>G(p.H656R)and the novel mutation first discovered in this research, the c.1694T>A (p.L565H). The mutations were mainly distributed in the exon 4, with the mutation frequency of 41; of them, patients with Avellino corneal dystrophy who carried the c.371G>A (p.R124H) mutation accounted for the greatest proportion (32/54). The average onset age of the 54 positive patients was 29.1±17.0 years (range 2-61 yeaes); Deposits could be seen from the corneal epithelium to the stroma layer in bilateral eye through the slit-lamp microscopy, and various mutations led to varied morphology of the corneal precipitates in patients.

Conclusions :
Our finding expand the spectrum of TGFBI mutation，a novel pathogenic mutation is discovered in this research, and it is re-confirmed that c.371G>A (p.R124H) is the most common mutation form in Asian patients with TGFBI genetic mutation-associated corneal dystrophy. Patients with corneal dystrophy show phenotypic heterogeneity, the corneal precipitate features are distinctly related to the genetic mutation that it carries, and the corneal dystrophy classification method based on the molecular genetics can improve the accuracy of clinical diagnosis.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.